1. Field of the Invention
The present invention relates to a haemofiltration machine for independently controlling the concentration of at least two ionic substances in a patient""s internal medium.
2. Background of the Invention
The present invention relates to a haemofiltration machine for independently controlling the concentration of at least two ionic substances in a patient""s internal medium.
The kidneys fulfil many functions, among which are the removal of water, the excretion of catabolites (or metabolic waste, such as urea and creatinine), the regulation of the concentration of ionic substances in the blood (sodium, potassium, magnesium, calcium, bicarbonates, phosphates and chlorides) and the regulation of the acid-base equilibrium of the internal medium, which is obtained in particular by removing weak acids (phosphates, monosodium acids) and by the production of ammonium salts.
In individuals who have lost the use of their kidneys, since these excretory and regulatory mechanisms no longer work, the internal medium becomes loaded with water and metabolic waste and has an excess of certain ionic substances (in particular sodium), as well as, in general, exhibiting acidosis, with the pH of the blood plasma shifting towards 7 (the blood pH normally varies within a narrow range of between 7.35 and 7.45).
To overcome the dysfunction of the kidneys, use is conventionally made either of dialysis or of haemofiltration, which are blood treatments administered by means of an exchanger with a semi-permeable membrane (haemodialysis machine/haemofilter) which is linked to the patient via an extracorporeal blood circulation circuit.
Dialysis consists in circulating, on either side of the exchanger membrane, the patient""s blood and a dialysis liquid comprising the main ionic substances of the blood, in concentrations close to those of the blood of a healthy individual. Moreover, a given volume of plasmatic water corresponding to the weight that the patient should lose during each dialysis session is made to flow by ultrafiltration through the membrane into the dialysis liquid compartment. The ultrafiltration results from a difference in pressure maintained between the two compartments of the exchanger delimited by the membrane.
The blood treatment which is carried out in the exchanger results from the diffusional transfer, across the membrane, of molecules of the same substance (ionic substances, metabolic waste) which are at different concentrations on either side of the membrane, the molecules migrating from the liquid in which they are at higher concentration to the liquid in which they are at lower concentration.
In a conventional dialysis machine, the dialysis liquid is prepared by means of a measured mixture of water and of two concentrated solutions, a first concentrated solution containing sodium chloride and sodium bicarbonate and the second concentrated solution containing calcium, potassium and magnesium chlorides as well as acetic acid. The role of the acetic acid is to limit the formation of calcium and magnesium carbonate precipitates which form unwanted deposits in the hydraulic circuit of the dialysis machine. Other dialysis devices have been proposed, in particular in documents EP 0 898 975 and EP 0 898 976, in which the dialysis liquid used contains no calcium or magnesium (as the respective bicarbonates) and in which a sodium bicarbonate solution (or a calcium or magnesium chloride solution, respectively) is infused into the patient. Irrespective of the type of dialysis administered, at the usual flow rate of dialysis liquid, i.e., 500 ml/min, 120 liters of dialysis liquid are prepared and used in the course of a four-hour dialysis session.
Haemofiltration consists in extracting from the blood circulating in the exchanger, by ultrafiltration, a large volume (up to thirty liters in the course of a four-hour session) of plasmatic water which is partially replaced by means of a simultaneous infusion of a sterile replacement liquid.
The blood treatment which is carried out in the exchanger results here from the convective transfer of molecules (ionic substances, metabolic waste) which are entrained by the plasmatic water which filters through the membrane under the effect of the pressure difference created between the two compartments of the exchanger.
The electrolyte composition of the replacement liquid used in haemofiltration is identical to that of a dialysis liquid. This liquid can be manufactured and packaged by a pharmaceutical laboratory in the form of two containers for two sterile liquids to be mixed together just before use, one of the containers containing all the bicarbonate and the other container containing all the calcium and magnesium. This replacement liquid can also be prepared at the time of use by filtration of a dialysis liquid, as is described in particular in document EP 0 622 087, the subject of which is a haemodiafiltration machine (combination of the two treatments defined above): in this machine, some of the dialysis liquid produced by a dialysis liquid generator is injected, after filtration, into the blood return tube of the extracorporeal circuit, while the rest of the dialysis liquid is circulated in the exchanger.
Despite its efficacy and its acknowledged superiority over dialysis in therapeutic terms (see, in particular, Long-term morbidity: Hemofiltration vs. Hemodialysis, by E. Quellhorst, U. Hildebrand, A. Solf, in Contrib. Nephrol. Basle, Karger, 1995, vol 113, pp. 110-119), the haemofiltration suffers from two limitations: a first limitation is associated with the cost of the treatment when the replacement liquid used is purchased ready-to-use. Since these sterile solutions packaged in split containers are expensive, the tendency is to limit the treatment administered to an exchange of liquids not exceeding thirty liters (i.e., a quarter as much as the volume of treatment liquid used during a dialysis session). The second limitation is that, even with a machine such as the one described in document EP 0 622 087 mentioned above, which provides replacement liquid at reduced cost, the exchange flow rate is limited since the ultrafiltration flow rate cannot be set at much more than a third of the flow rate of the blood in the extracorporeal circuit.
In the light of the foregoing considerations, one aim of the invention is to produce a system for treating renal insufficiency which makes it possible to carry out a haemofiltration session in the course of which very large volumes of liquid can be exchanged, without this haemofiltration session being any longer or any more expensive than a conventional dialysis session, and also without it displaying the known drawbacks relating to the preparation of an unstable treatment liquid.
In accordance with the invention, this aim is achieved by means of a haemofiltration machine designed to cooperate with a haemofilter having a first compartment and a second compartment separated by a semi-permeable membrane, the first compartment having an inlet which can be connected to a blood withdrawing tube and an outlet which can be connected to a blood return tube, and the second compartment having an outlet which can be connected to a spent liquid evacuation tube. This haemofiltration machine comprises means for preparing a first injectable solution from at least one concentrated solution; means for injecting, at an injection flow rate Qpre, the first solution into the blood withdrawing tube; means for infusing into the blood return tube a second solution containing at least one ionic substance A having a given concentration [A]post which is different from the concentration [A]pre of this substance A in the first solution; means for determining an infusion flow rate Qpost of the second solution in order for the concentration of the substance A in the patient""s internal medium to tend towards a desired concentration [A]des, as a function of the concentration [A]post of the substance A in the second solution, the desired concentration [A]des, the injection flow rate Qpre of the first solution and the blood flow rate QB; and control means for governing the infusion means such that the flow rate of the second solution is substantially equal to the determined flow rate Qpost.
The invention makes it possible to achieve the pursued aim since, as the first solution is injected upstream of the exchanger, the blood which penetrates into the exchanger is diluted such that the proportion of this mixture which can be ultrafiltered is very much higher than the admissible proportion when the blood is not diluted. Consequently, it is possible with this machine to envisage administering a treatment in the course of which fifty to eighty liters of treatment liquid are exchanged against the same volume of plasmatic water. Moreover, dilution of the blood reduces the drawbacks associated with the viscosity of the total blood, i.e., the resistance to flow and the hindrance to transfers, and it reduces the risks of clotting in the exchanger since the concentration of clotting factors therein is reduced. The ultrafiltration of a diluted blood is also less traumatic for the components present in the blood than the ultrafiltration of undiluted blood.
This system also has the advantage in that the respective concentrations of at least two ionic substances forming part of the composition of a replacement liquid can be controlled independently of each other, which is often desirable at least for sodium, potassium or bicarbonate.
According to one characteristic of the invention, the substance A is absent from the first solution and the means for determining the infusion flow rate Qpost comprise calculation means for calculating the infusion flow rate Qpost according to the formula:                               Q          post                =                                                            [                A                ]                            des                        xc3x97                          Q              B                        xc3x97                          Q              pre                                                                                            [                  A                  ]                                post                            xc3x97                              Q                B                                      +                                                            [                  A                  ]                                post                            xc3x97                              Q                pre                                      -                                                            [                  A                  ]                                des                            xc3x97                              Q                B                                                                        (        1        )            
According to one embodiment of the invention, the first or second solution contains bicarbonate and contains no magnesium or calcium, while the other solution contains magnesium and calcium and contains no bicarbonate.
By means of separating the bicarbonate, on the one hand, and the magnesium and calcium, on the other hand, it is unnecessary to add acetic acid to either of the solutions to avoid the formation of unwanted precipitates, and this has obvious advantages as regards the devices used for preparing the solutions, which are not exposed to corrosion due to the action of an acid, or to encrustation due to carbonate-based deposits. Moreover, the absence of acid from the first solution is desirable in therapeutic terms since it appears that the dilution of blood with a liquid whose pH is less than that of blood is one of the co-factors of certain hypersensitivity reactions.
Another advantage of the invention lies in the possibility of continuously determining and adjusting the flow rate of the second solution, in particular when this solution contains all the calcium, magnesium and potassium infused into the patient. Specifically, it is known that an excess, much like a deficit, of potassium, calcium or magnesium in the blood can give rise to serious disorders in the patient, in particular heart disorders. Now, ultrafiltration of the blood brings about the convective removal of some of the ionic substances in the diluted blood which circulates in the exchanger, and this convective loss varies as a function of the parameters of the treatment which are modified in the course of treatment, such as the flow rate of the first solution and the flow rate of the blood. By virtue of the means, possessed by the haemofiltration machine according to the invention, for determining the flow rate of the second solution, it is possible to continuously compensate for the variable convective losses which arise in the exchanger.
The infusion, downstream of the exchanger or directly in the patient, of a second solution containing all the calcium infused into the patient, also has a further advantage resulting from the depletion of calcium from the diluted blood in the exchanger: it is known that ionic calcium is involved in the cascade of reactions constituting the blood-clotting process. Massive depletion of calcium from the blood in the exchanger thus partially inhibits the clotting process, thereby making it possible to reduce the amount of anticoagulant injected into the extracorporeal blood circulation circuit to prevent the blood from clotting therein.
Other characteristics and advantages of the invention will become more apparent on reading the description which follows.